Table 1.

Examples of modifications of CTCAE v4.03 and rationale

ExampleRationale for modificationCTCAE v4.03Modified CTCAE v4.03
CTCAE v4.03 Eye disorders: Other, specify Visual field deficit“Visual field deficit” is not specifically included as an adverse event in CTCAE v4.03. Option of “other” eye disorders is not specific without incorporating patient-reported outcomes relative to performance of ADLs. Grade 4 is eliminated, because visual field deficits represented persistent (as opposed to acute) events in long-term survivor cohort.
  1. Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated

  2. Moderate; minimal, local, or noninvasive intervention indicated; limiting age appropriate instrumental ADL

  3. Severe or medically significant, but not immediately sight threatening; hospitalization or prolongation of existing hospitalization indicated; disabling; limiting self-care ADL

  4. Sight-threatening consequences; urgent intervention indicated; blindness (20/200 or worse) in affected eye

  1. Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated

  2. Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental ADL (unable to drive)

  3. Severe or medically significant, but not immediately sight threatening; hospitalization or prolongation of existing hospitalization indicated; disabling; limiting self-care ADL (unable to ambulate/navigate)

  4. Not applicable

CTCAE v4.03 Infections and infestations: Hepatitis viralWith availability of more effective therapy for chronic hepatitis, “Grade 1: asymptomatic; treatment not indicated” was perceived to be inappropriate, as symptoms are not the only indication driving treatment decisions. Grade 2 category developed to reflect common presentation with asymptomatic hepatitis and variceal hemorrhage to reflect decompensated liver function. Additional text added to Grade 3 to align with proposed CTCAE v5.0.
  1. Asymptomatic, treatment not indicated

  2. Not applicable

  3. Symptomatic liver dysfunction; fibrosis by biopsy; compensated cirrhosis

  4. Decompensated liver function (e.g., coagulopathy, encephalopathy, coma)

  5. Death

  1. Asymptomatic

  2. Asymptomatic but treated with antiviral therapy

  3. Symptomatic liver dysfunction; fibrosis by biopsy; compensated cirrhosis: hospitalization or prolongation of existing hospitalization indicated

  4. Decompensated liver function (e.g., coagulopathy, encephalopathy, coma, variceal hemorrhage)

  5. Death

CTCAE v4.03 Nervous system disorders: Intracranial hemorrhageText added to clarify neuroimaging findings consistent with intracranial bleeding in asymptomatic survivors.
  1. Asymptomatic; clinical or diagnostic observations only; intervention not indicated

  2. Moderate symptoms; medical intervention indicated

  3. Ventriculostomy, ICP monitoring, intraventricular thrombolysis, or operative intervention indicated

  4. Life-threatening consequences; urgent intervention indicated

  5. Death

  1. Asymptomatic; clinical or diagnostic observations only; intervention not indicated (MRI evidence of microhemorrhage, e.g., hemosiderin)

  2. Moderate symptoms; medical intervention indicated

  3. Ventriculostomy, ICP monitoring, intraventricular thrombolysis, or operative intervention indicated

  4. Life-threatening consequences; urgent intervention indicated

  5. Death

CTCAE v4.03 Respiratory, thoracic, and mediastinal disorders: BronchospasmText added to clarify integration of routine clinical management into severity grading.
  1. Mild symptoms; intervention not indicated

  2. Symptomatic; medical intervention indicated; limiting instrumental ADL

  3. Limiting self-care ADL; oxygen saturation decreased

  4. Life-threatening respiratory or hemodynamic compromise; intubation or urgent intervention indicated

  5. Death

  1. Mild symptoms; intervention not Indicated

  2. Symptomatic; medical intervention indicated; limiting instrumental ADL; intermittent asthma requiring short-acting beta agonists as needed

  3. Limiting self-care ADL; oxygen saturation decreased; persistent asthma requiring daily controller medication (oral or inhaled)

  4. Life-threatening respiratory or hemodynamic compromise; intubation or urgent intervention indicated

  5. Death

CTCAE v4.03 Investigations: Ejection fraction decreasedEjection fraction parameters specified to denote subnormal range and clinically significant decline from baseline. Text added to clarify integration of routine clinical management into severity grading.
  1. Not applicable

  2. Resting EF 50%–40%; 10%–19% drop from baseline

  3. Resting EF 39%–20%; >20% drop from baseline

  4. Resting EF <20%

  5. Death

  1. Not applicable

  2. Resting EF less than 50%–40%; 10%–19% absolute drop from baseline

  3. Resting EF 39%–20%; >20% absolute drop from baseline; medication indicated or initiated

  4. Resting EF <20%; refractory or poorly controlled heart failure due to drop in ejection fraction; intervention such as ventricular assist device, intravenous vasopressor support, or heart transplant indicated

  5. Death

CTCAE v4.03 Metabolism and nutrition disorders: Glucose intolerance (includes impaired fasting glucose, insulin resistance with impaired glucose tolerance, diabetes mellitus)Text added to clarify integration of routine clinical management into severity grading.
  1. Asymptomatic; clinical or diagnostic observations only; intervention not indicated

  2. Symptomatic; oral agent indicated

  3. Severe symptoms; insulin indicated

  4. Life-threatening consequences; urgent intervention indicated

  5. Death

  1. Asymptomatic; clinical or diagnostic observations only; pharmacologic intervention not indicated or initiated (e.g., dietary modification)

  2. Symptomatic; oral agent indicated or initiated

  3. Severe symptoms; insulin indicated or initiated

  4. Life-threatening consequences; urgent intervention indicated or initiated

  5. Death

  • Abbreviations: ADL, activities of daily living; ICP, intracranial pressure.